Feeding rats diets containing oils that have a low alpha-linolenic acid [18:3(n-3)] content, such as sunflower oil, results in reduced amounts of docosahexaenoic acid [22:6(n-3)] in all brain cells and organelles compared to rats fed a diet containing soybean oil or rapeseed oil. During the period of cerebral development there is a linear relationship between the n-3 fatty acid content of the brain and that of food until alpha-linolenic acid represents approximately 200 mg/100 g food [0.4% of the total dietary energy for 18:3(n-3)]. Beyond that point brain levels reach a plateau. Similar values are also found for other organs. The level of 22:6(n-3) in membranes is little affected by the dietary quantity of linoleic acid [18:2(n-6)] if 18:3(n-3) represents approximately 0.4% of energy. In membranes from rats fed diets containing sunflower oil, Na+, K(+)-ATPase activity in nerve terminals was 60%, 5'-nucleotidase in whole brain homogenate was 80%, and 2',3'-cyclic nucleotide 3'-phosphodiesterase was 88% of that in membranes from rats fed diets containing soybean oil. A diet low in alpha-linolenic acid leads to anomalies in the electroretinogram, which partially disappear with age. It has little effect on motor activity, but it seriously affects learning tasks as measured with the shuttle box test. Rats fed a diet low in alpha-linolenic acid showed an earlier mortality in response to an intraperitoneal injection of a neurotoxin, triethyltin, than did rats fed a normal soybean oil diet.

Rats were fed through four generations with a semisynthetic diet containing 1.0% sunflower oil (6.7 mg/g n-6 fatty acids, 0.04 mg/g n-3 fatty acids). Ten days before mating, half of the animals received a diet in which sunflower was replaced by soya oil (6.6 mg/g n-6 fatty acids, 0.8 mg/g n-3 fatty acids) and analyses were performed on their pups. Fatty acid analysis in isolated cellular and subcellular material from sunflower-fed animals showed that the total amount of unsaturated fatty acids was not reduced in any cellular or subcellular fraction (except in 60-day-old rat neurons). All material from animals fed with sunflower oil showed an important reduction in the docosahexaenoic acid content, compensated (except in 60-day-old rat neurons) by an increase in the n-6 fatty acids (mainly C22:5 n-6). When comparing 60-day-old animals fed with soya oil or sunflower oil, the n-3/n-6 fatty acid ratio was reduced 16-fold in oligodendrocytes, 12-fold in myelin, twofold in neurons, sixfold in synaptosomes, and threefold in astrocytes. No trienes were detected. Saturated and monounsaturated fatty acids were hardly affected. This study provides data on the fatty acid composition of isolated brain cells.

Objective-Blood flow is altered in metabolic and ischemic diseases with dramatic consequences. Resistance arteries structure and function remodel in response to chronic blood flow changes through a mechanism remaining mainly unknown. We hypothesized that the NO pathway and matrix metalloproteases (MMPs) activation might play a role in flow (shear stress)-induced microvascular remodeling. Methods and Results-Mesenteric resistance arteries were ligated to alter blood flow in vivo for 4 or 14 days: arteries were submitted to high (HF), low (LF), or normal flow (NF). Rats were treated with L-NAME, the angiotensin converting enzyme inhibitor perindopril or the MMPs inhibitor doxycycline. After 14 days, outward hypertrophic remodeling occurred in HF arteries in association with eNOS overexpression. MMP9 activity increased in the early phase (day 4). HF-remodeling was prevented by L-NAME, eNOS gene knockout, and doxycycline. L-NAME prevented eNOS overexpression and MMPs activation whereas doxycycline only prevented MMPs activation. In LF arteries diameter reduction was associated with a decreased eNOS expression without change in MMPs expression and activation. LF-remodeling was reduced by perindopril. Key Words: microcirculation (resistance arteries) Ⅲ remodeling Ⅲ blood flow Ⅲ shear stress Ⅲ endothelium Ⅲ nitric oxide Ⅲ matrix metalloproteases C ardiac output generates blood flow in large compliance arteries followed by small resistance muscular arteries able to adapt their diameter to the metabolic need of the downstream located tissues. Resistance arteries are subjected to mechanical forces, pressure, and flow (shear stress), inducing respectively myogenic tone and flow-dependent dilation. 1 Flow stimulates the endothelium to produce contractile (PGH 2 , TXA 2 , endothelin, reactive oxygen species) and relaxing factors including nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin (PGI 2 ). Long-term changes in blood flow induce arterial wall remodeling to normalize shear stress. In large conductance arteries, remodeling is associated with neointimal hyperplasia 2 and depends on NO production 3 and matrix metalloprotease (MMP) activation. 4 In arterioles or resistance arteries, flow-dependent remodeling is involved in physiological processes, such as blood vessel growth during development, 5 exercise training, 6 or pregnancy 7 and in pathological situations including hypertension, 8 diabetes, 9 ischemic diseases, 10 or tumor growth. Conclusions-InIn resistance arteries blood flow reduction induces inward remodeling and reduced contractile capacity whereas chronic increases in blood flow triggers outward hypertrophic remodeling. 11,12,13 The mechanisms involved in flow-induced remodeling have been mainly investigated in large elastic arteries and in cultured endothelial cells which may not be relevant for arterioles in vivo. 3 Studies in small arteries show the central role of shear stress, 14 circumferential wall stress, 12,15 transient dedifferentiation, and turnover of smooth mus...